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Aim: Study first-line (1L) treatment patterns and economic outcomes among patients with advanced metastatic gastric cancer (GC) and esophageal cancer (EC). Materials & methods: Newly diagnosed patients with systemic GC and EC treatments were identified between 1 January 2011 and 31 July 2017; costs were presented as per patient per month (PPPM) basis. Results: Study included 392 GC and 436 EC patients. Most frequently used 1L regimens were: 5-fluorouracil (5-FU) + oxaliplatin (22.5%) and epirubicin + cisplatin + 5-FU (ECF)/ECF modifications (21.9%) in patients with GC; and carboplatin + paclitaxel (29.6%) and 5-FU + oxaliplatin (11.5%) in EC patients. Mean all-cause costs were US$16,242 PPPM for GC, and $18,384 PPPM for EC during 1L treatment. Conclusion: GC and EC were resource intensive and costly. High costs and short treatment durations underscored a gap in care in 1L treatment.

Gastric cancer is the one of the most lethal malignancies of digestive system. Identifying molecular biomarkers is invaluable in help predicting clinical outcomes and developing targeted chemotherapies. GINS complex subunit 2 (GINS2) plays an essential role in the initiation and elongation of DNA replication. Although there have been studies revealing the prognostic significance of GINS2 in breast cancer and lung cancer, its involvement and function in gastric cancer need to be elucidated. We retrospectively enrolled a cohort of gastric adenocarcinoma patients after surgical resection (n = 123). By analyzing the mRNA and protein levels of GINS2 in tissue samples, we found that GINS2 presented a higher expression in tumor tissues than in adjacent normal stomach tissues. Besides, GINS2 level was positively correlated with tumor size and gastric adenocarcinoma tumor stage, implying its potential role as a tumor promoter. Univariate and multivariate analyses identified that patients with lower GINS2 showed a better overall survival compared to those with higher GINS2 expression. In addition, cellular and xenograft experiments confirmed the role of GINS2 in facilitating tumor proliferation both in vitro and in vivo. To our knowledge, this is the initial finding on GINS2 in promoting gastric adenocarcinoma progression. In conclusion, our study revealed a pro-oncogenic role of GINS2 in gastric cancer.

Based on the analysis of the research status of university teachers' data literacy at home and abroad, combined with the survey results of university teachers' data literacy ability in China, this paper uses data classification and other methods to mine the core elements of university teachers' data literacy ability; Further use the scoring method to build a multi-level dynamic evaluation system of teachers' data literacy ability; For different levels of data literacy capabilities, we will build a multi-level promotion strategy plan to form a complete set of dynamic strategies for improving college teachers' data literacy capabilities, and promote and apply them.

BACKGROUND Multimorbidity represents a global health challenge, which requires a more global understanding of multimorbidity patterns and trends. However, the majority of studies completed to date have often relied on self-reported conditions, and a simultaneous assessment of the entire spectrum of chronic disease co-occurrence, especially in developing regions, has not yet been performed. OBJECTIVE We attempted to provide a multidimensional approach to understand the full spectrum of chronic disease co-occurrence among general inpatients in southwest China, in order to investigate multimorbidity patterns and temporal trends, and assess their age and sex differences. METHODS We conducted a retrospective cohort analysis based on 8.8 million hospital discharge records of about 5.0 million individuals of all ages from 2015 to 2019 in a megacity in southwest China. We examined all chronic diagnoses using the ICD-10 (International Classification of Diseases, 10th revision) codes at 3 digits and focused on chronic diseases with ≥1% prevalence for each of the age and sex strata, which resulted in a total of 149 and 145 chronic diseases in males and females, respectively. We constructed multimorbidity networks in the general population based on sex and age, and used the cosine index to measure the co-occurrence of chronic diseases. Then, we divided the networks into communities and assessed their temporal trends. RESULTS The results showed complex interactions among chronic diseases, with more intensive connections among males and inpatients ≥40 years old. A total of 9 chronic diseases were simultaneously classified as central diseases, hubs, and bursts in the multimorbidity networks. Among them, 5 diseases were common to both males and females, including hypertension, chronic ischemic heart disease, cerebral infarction, other cerebrovascular diseases, and atherosclerosis. The earliest leaps (degree leaps ≥6) appeared at a disorder of glycoprotein metabolism that happened at 25-29 years in males, about 15 years earlier than in females. The number of chronic diseases in the community increased over time, but the new entrants did not replace the root of the community. CONCLUSIONS Our multimorbidity network analysis identified specific differences in the co-occurrence of chronic diagnoses by sex and age, which could help in the design of clinical interventions for inpatient multimorbidity.

Recent developments in novel spatial sequencing technologies allow for the incorporation of spatial information into high-throughput sequencing assays. One such method, Deterministic Barcoding in Tissue for spatial omics sequencing (DBiT-seq, abbreviated herein as DBiT), utilizes perpendicular microfluidic channels to deliver DNA barcodes across the tissue in a spatially-encoded manner, allowing for sequenced reads to be mapped back onto the 2-D coordinates of the tissue to provide spatial coordinates to cells. DBiT has been the first spatial sequencing technology developed for epigenomic assays beyond transcriptome and proteome. However, despite existing of many open-source software packages for downstream bioinformatics analysis, there is no software available for processing DBiT image data with evenly spaced channels. To facilitate the integration of DBiT spatial and sequenced data, here we proposed a new method to precisely capture the spatial information and further developed AtlasXbrowser based on the new method to extract spatial data from the image data.AtlasXbrowser is a python-based tool with GUI that requires no technical expertise to operate and enables researchers to incorporate brightfield and epifluorescence images of processed tissue samples into downstream bioinformatics analysis tools.Availability and implementationFreely available at https://github.com/atlasxomics/AtlasXbrowser.

BACKGROUND AND AIMS Circulating histones play a crucial role in the development and progression of sepsis and is associated with high mortality. Hemadsorption with the CytoSorb® filter has been shown to non-specifically eliminate systemic circulating histones in plasma from injured patients ex vivo and in vitro. The aim of this study was to fabricate another novel hemoperfusion adsorbent for selective removal of histones in the blood of septic patients. METHOD Chitosan-cellulose composite hydrogels (CSCE) were first prepared using a liquid-liquid inversion method. Then, negatively charged heparin was grafted onto the surfaces of the CSCE hydrogels by EDC chemistry to obtain the histone sorbents (CSCEHEP hydrogels). The chemical structure of CSCEHEP hydrogels was characterized by Fourier transform infrared spectroscopy (FTIR) and its hemocompatibility was evaluated. The adsorption capacity and adsorption selectivity of CSCEHEP hydrogels for histone were then analysed by BCA protein quantitative method. Besides, the antagonistic effect of CSCEHEP hydrogels on histone-induced cytotoxicity was verified by in vitro cell experiments using HK-2 cell lines. RESULTS The obtained CSCEHEP hydrogels showed characteristic adsorption peaks of the sulfonic group at 1217 and 940 cm-1 in their FTIR spectrum, suggesting the successful immobilization of heparin onto the surface of the sorbent. The clotting time of plasma after a 30-min incubation with CSCEHEP hydrogels was significantly prolonged by 3 times while no obvious hemolysis, platelet activation, complement activation and other blood-material adverse reactions occurred during this incubation. With a heparin grafting, the adsorption capacity of CSCEHEP hydrogels towards histones (from calf thymus) increased significantly to 314.3 μg/g, with a clearance rate of 62.8%, compared to that of pristine CSCE, which is dependent on the initial histone concentrations in testing solutions. On the contrary, the adsorption capacity of bovine serum albumin by CSCEHEP hydrogels was significantly lower than that of histones, suggesting that the adsorption process of histone by CSCEHEP in plasma was selective. Meanwhile, CSCEHEP hydrogels significantly antagonized histone-induced cytotoxicity by binding histones, and the cell viability increased significantly from 47.1% (model group) to 72.0% (CSCEHEP-treat group). CONCLUSION CSCEHEP hydrogels are of good hemocompatibility and can effectively adsorb histones in PBS solution and antagonize histone-induced cytotoxicity. It is believed that the use of such a histone sorbent for extracorporeal blood purification may provide a novel insight into the modulation of aberrant immune responses in patients with sepsis.

BACKGROUND AND AIMS Vascular calcification can occur in the early stages of chronic kidney disease (CKD) and result in a poor prognosis. How the calcification signal in the blood is transduced from endothelial cells in the tunica intima to vascular smooth muscle cells in the tunica media in the early stages of CKD is still unknown. The aim of this study was to explore the role of exosomes in signal transduction in vascular calcification. METHOD Exosomes were isolated from normal phosphate- and high phosphate-stimulated human umbilical vein endothelial cells (HUVECs) by superspeed centrifugation. We used transmission electron microscopy, molecular size analysis and Western blot analysis of exosome markers to identify exosomes (Figure 1). VSMC calcification was assessed by Alizarin Red Staining and Western blot. Proteomics analysis and miRNA microarray analysis were carried out to detect the differences in exosomal proteins and miRNAs. The results were analysed via Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. RESULTS Fluorescence microscopy verified that VSMCs took up exosomes from HUVECs. Exosomes isolated from high phosphate-stimulated HUVECs (HP-HUVEC-exos) induced VSMC calcification (assessed by Alizarin Red Staining), increased osteopontin expression and increased alkaline phosphatase activity (Figure 2). Proteomics analysis showed different protein expressions including STAT1, STAT3, HDAC1, PARP1, WDR5 et al. MiRNA microarray analysis showed different miRNA levels including miR-223–3p, miR-6776–5p, miR-6851–5p, miR-2116–3p, miR-6849–5p et al. (Figure 3). Target GO analysis showed that both miRNA and protein difference focused on some biological processes (RNA splicing, mRNA processing, RNA targeting), molecular function (cadherin binding, cell adhesion molecule binding, ubiquitin-like protein ligase binding) and cellular component (focal adhesion, cell-substrate junction, spliceosomal complex). KEGG analysis revealed that both miRNA and protein differences were focused on pathways associated with the cell cycle, virus infection and protein processing in the endoplasmic reticulum. CONCLUSION Exosome-mediated miRNA and protein transfer from endothelial cells to VSMCs may induce vascular calcification via RNA processing, protein processing and cell adhesion.

Facing the existing digital image libraries on landscape, researchers need to urgently solve a challenging problem: how to realize rational management and accurate retrieval of landscape images that contain feature information like hierarchy, layout, color system, and color matching. For accurate organization and labeling of landscape Images, this paper presents a novel method for feature extraction and image retrieval of landscape images based on image processing. Firstly, a color quantization process was designed for landscape images, and used to analyze the color composition and color space pattern (CSP) of such images. Next, the existing methods, which are suitable for the extraction of color features from landscape Images, were briefly reviewed, and the basic flows of our improved algorithm and division method of landscape color blocks (LCBs) were explained. Finally, the retrieval performance of landscape images was improved by matching of weighted color blocks of regional landscape, based on the multi-dimensional color eigenvectors of landscape image. The experimental results demonstrate the effectiveness of our algorithm. The research results shed light on the feature extraction from other types of color images.

Early pregnancy loss (EPL) is a common event worldwide. Previous studies show that mitochondrial DNA (mtDNA) copy number (CN) is associated with semen parameters and preimplantation embryo viability, indicating the predictive potential of mtDNA CN for ongoing pregnancy outcomes. However, no relevant study has assessed the relationship between mtDNA CN and EPL. Thus, we aimed to determine whether mtDNA CN and mtDNA 4977-bp deletion rate (DR) in chorionic villous tissue are associated with EPL. Chorionic villous tissue total DNA was extracted from 75 EPL cases and 75 healthy controls. Chromosomal analysis was conducted using copy number variation (CNV) sequencing. The mtDNA CN and DR were measured in samples without pathogenic CNVs. The association between mtDNA CN or DR and EPL risk were estimated using logistic regression. The EPL group had a significantly different mtDNA CN (P 0.001) and DR (P = 0.005) compared to the control group. Both biomarkers were independent risk factors for EPL (CN odds ratio 1.71, 95% confidence interval 1.17 to 2.49, P = 0.005; DR odds ratio 1.07, 95% confidence interval 1.02 to 1.12, P = 0.006). These results suggest that higher mtDNA CN and DR levels are strongly associated with EPL and represent independent risk factors for EPL. Further studies validating these findings and exploring the underlying biological mechanisms are warranted.

Coordination polymers (CPs) have attracted considerable attention for use in noble-metal-free electrochemical water splitting, for example, by the hydrogen/oxygen evolution reactions (HER/OER). Tra...

Background: A rapid and simple analytical method for the screening and quantification of multi-residues was established by a quick, easy, cheap, effective, rugged and safe (QuEChERS) approach coupled to ultra-performance liquid chromatography and electrospray ionization quadrupole orbitrap high-resolution mass spectrometry (UPLC-Q-Orbitrap HRMS). A total number of 59 veterinary drugs were investigated, which belonged to 12 classes, such as β-agonist, quinolones, sulfonamides, tetracyclines, lincomycin series, triphenylmethane, nitroimidazoles, macrolides, amide alcohols, quinoxalines, steroid hormone and sedatives. Methods: The factors which influence the determination of veterinary drugs residues, such as mobile phase, extract solvent, clean up sorbent, and re-dissolved solvent, were optimized by the single factor experiment. The method was sufficiently validated by using the parameters of linearity, sensitivity, accuracy, and repeatability. Results: The response of the detector was linear for 59 veterinary drug residues in extensive range (two to three orders of magnitude) with a high coefficient of determination (R2) (0.9995-0.9998). The limit of quantification (LOQ) ranged from 0.1μg/kg to 2.0μg/kg for 59 veterinary drug residues in pork samples. The repeatability was in the range of 1.0%-9.5%. Average recoveries of 59 veterinary drugs at three spiked levels ranged from 53.7%-117.8% with relative standard deviation (RSD) of 1.9%-13.9%. The full MS scan coupled with data-dependent MS/MS mode was applied for screening the target compounds to simultaneously obtain the accurate mass of parent ion and the mass spectrum of fragments. Elemental composition, accurate mass, and retention time and characteristic fragment ions were used to establish a homemade database. Conclusion: The ability of the homemade database was verified by analyzing the real pork samples, and the result was satisfactory.

Purpose The aim of this study was to investigate the clinical characteristics and management of malignant ovarian tumors during pregnancy, as well as the feto-maternal outcomes and analyze the influential factors on the pregnancy outcomes. Patients and Methods Eighty-five patients with ovarian malignancies during pregnancy treated at 12 tertiary hospitals between 2009 and 2019 were analyzed in this study. The clinical features, histopathological characteristics, clinical management, and maternal and perinatal outcomes were retrospectively analyzed. The clinical features and managements were compared between abortion group and live birth group. Results The following diagnoses were made: 41 (48.24%) patients with borderline ovarian tumors, 18 (21.18%) patients with epithelial ovarian cancers, 17 (20.00%) patients with non-epithelial ovarian malignancies and 9 (10.59%) patients with metastatic ovarian tumors. Thirty-six (42.45%) patients underwent conservative surgical treatment. Thirty-four (40.00%) patients opted for fertility-sparing surgery, and fifteen (17.56%) patients received radical surgery. Chemotherapy was administered to 32.94% of the patients. The proportion of ovarian malignancies diagnosed in the first trimester in the abortion group was higher than that in the live birth group (P

With the extensive application of Internet of things technology and visual object tracking technology in various neighborhoods, the traditional visual object tracking algorithm can no longer meet the needs of Internet of things. The Internet of things with its powerful perception, multi-information transmission ability and super intelligent processing ability force the traditional visual object tracking algorithm to innovate and improve. In order to improve the tracking algorithm’s ability to cope with complex and drastic changes in the target’s appearance, in this paper, an accurate and robust visual object tracking algorithm (visual object tracking) based on K-means clustering algorithm on the integrated model ENS is studied. The tracking target is divided into several sample packets, and the size of the sample packet is compressed to match different weights of the filter in frequency domain. Finally, a more accurate and robust filter is built to realize the tracking of the target. Experimental simulation results show that the improved visual object tracking algorithm ENS-CSK approximately conforms to two-dimensional gaussian distribution in tracking effect, and the tracking success rate and accuracy are higher than the AdaBoost algorithm and KCF algorithm mentioned in the paper. Therefore, the improved visual object tracking algorithm ENS-CSK algorithm in this paper can better match the visual object tracking under the Internet of things technology. Therefore, it can be extended to the process of ore phase transformation of pellet under continuous calcination with varying temperature. Thus, the pressure resistance of pellets at different calcining temperatures can be predicted more accurately.

Recent advances in Bionano optical mapping (BOM) provide a great insight into the determination of structural variants (SVs), but its utility in identification of clinical likely pathogenic variants needs to be further demonstrated and proved. In a family with two consecutive pregnancies affected with ventriculomegaly, a splicing likely pathogenic variant at the LAMA1 locus (NM_005559: c. 4663 + 1 G > C) inherited from the father was identified in the proband by whole-exome sequencing, and no other pathogenic variant associated with the clinical phenotypes was detected. SV analysis by BOM revealed an ~48 kb duplication at the LAMA1 locus in the maternal sample. Real-time quantitative PCR and Sanger sequencing further confirmed the duplication as c.859-153_4806 + 910dup. Based on these variants, we hypothesize that the fetuses have Poretti-Boltshauser syndrome (PBS) presenting with ventriculomegaly. With the ability to determine single nucleotide variants and SVs, the strategy adopted here might be useful to detect cases missed by current routine screening methods. In addition, our study may broaden the phenotypic spectrum of fetuses with PBS.

An increasing utilization of flexible healthcare electronics and biomedicine-related therapeutic materials urges the development of multifunctional wearable/flexible smart fabrics for personal therapy and health management. However, it is currently a challenge to fabricate multifunctional and on-body healthcare electronic devices with reliable mechanical flexibility, excellent breathability, and self-controllable joule heating effects. Here, we fabricate a multifunctional MXene-based smart fabric by depositing 2D Ti3C2Tx nanosheets onto cellulose fiber nonwoven fabric via special MXene-cellulose fiber interactions. Such multifunctional fabrics exhibit sensitive and reversible humidity response upon H2O-induced swelling/contraction of channels between the MXene interlayers, enabling wearable respiration monitoring application. Besides, it can also serve as a low-voltage thermotherapy platform due to its fast and stable electro-thermal response. Interestingly, water molecular extraction induces electrical response upon heating, i.e., functioning as a temperature alarm, which allows for real-time temperature monitoring for thermotherapy platform without low-temperature burn risk. Furthermore, metal-like conductivity of MXene renders the fabric an excellent Joule heating effect, which can moderately kill bacteria surrounding the wound in bacteria-infected wound healing therapy. This work introduces a multifunctional smart flexible fabric suitable for next-generation wearable electronic devices for mobile healthcare and personal medical therapy.

5-(3,4-Dicarboxylphenyl) picolinic acid (H3dppa) was applied as a new building block for the synthesis of two isomorphic coordination polymers, namely [Ni1.5dppa(H2O)3]n·nH2O (1), [Co1.5dppa(H2O)3]n·nH2O (2). Two compounds were generated by a hydrothermal self-assembly method using the corresponding metal(II) acetates and H3cppa ligand. Structure analysis reveals that compounds 1 and 2 are isomorphic both featuring a two-dimensional wave structure and are finally extended into the three-dimensional supramolecular architecture though hydrogen bonding interactions. Magnetic susceptibility measurements indicate that domain a weak ferromagnetic exchange coupling between the adjacent Ni(II) centers in 1, and a weak antiferromagnetic coupling between Co(II) ions in for 2.

Although tumor-associated macrophages (TAMs) have been shown to promote cancer progression, their roles in tumor development and resistance to therapy remain to be fully understood, mainly because of the lack of a good approach to evaluate the dynamic changes of heterogeneous macrophages in their residing microenvironment. Here, we report an approach of using antibiofouling PEG-b-AGE polymer-coated iron oxide nanoparticles (IONPs) for targeted imaging of mannose receptor (CD206)-expressing M2-like TAMs. Antibiofouling polymer coatings block non-specific phagocytosis of IONPs by different cells but enable ligand-mediated CD206(+) M2-like macrophage targeting after surface functionalizing with mannose (Man-IONP). Costaining tissue sections of the 4T1 mouse mammary tumors using an anti-CD206 antibody and fluorescent dye (TRITC)-labeled Man-IONP showed 94.7 ± 4.5% colocalization of TRITC-Man-IONPs with the anti-CD206 antibody. At 48 h after intravenous (i.v.) injection of Man-IONPs, magnetic resonance imaging of mice bearing orthotopic 4T1 mammary tumors showed a significantly larger IONP-induced decrease of the transverse relaxation time (T(2)) in tumors with 29.4 ± 1.5 ms compared to 12.3 ± 3.6 ms in tumors that received non-targeted IONP probes (P < 0.001). Immunofluorescence-stained tumor tissue sections collected at 6, 18, and 24 h after i.v. administration of the nanoprobes revealed that Man-IONPs specifically targeted CD206(+) M2-like macrophages in various tumor areas at all time points, while nonconjugated IONPs were absent in the tumor after 18 h. Thus, antibiofouling Man-IONPs demonstrated the capability of explicitly imaging CD206(+) M2-like macrophages in vivo and potentials for investigating the dynamics of macrophages in the tumor microenvironment and delivering therapeutics targeting M2-like TAMs.

Sperm DNA fragmentation index (SDF), as an important supplement to routine semen parameters, has been proposed to discriminate between fertile and infertile men, and predicts the outcomes of natural conception and in vitro fertilization. Unfortunately there are uncertainty and contradictory evidences regarding the importance of SDF. An important reason is the fact that significant and fundamental research about SDF is rare. This study was designed to characterize the microRNA (miRNA) expression profile in seminal plasma of normospermic patients with different SDF and their implications in human fertility. Using next-generation sequencing (NGS), a total of 897 human miRNAs were detected from 10 seminal plasma samples, out of which 431 differentially expressed miRNAs in 5 pairs of seminal plasma samples (each pair of seminal plasma samples obtained from the same male), with 14 miRNAs were identified in all the pairs. According to the fold change and expression level, 7 miRNAs including miR-374b-5p, miR-429, hsa-miR-26b-5p, miR-21-5p, miR-4257, miR-135b-5p and miR-134-5p were selected for further excavation. MiR-374b-5p and miR-26b-5p were significantly different in 3 sets of individual seminal plasma samples with different SDF from total 90 infertile patients (30 patients each set). Our results demonstrate that the profile of miR-374b and miR-26b with significantly decreased expression could be used as a first indication of increased SDF. And miR-374b and miR-26b could serve as adjunct biomarkers for the diagnosis of idiopathic infertile males.

BackgroundElevated serum uric acid concentrations have been associated with metabolic syndrome. However, only limited information is available on the prevalence of hyperuricaemia in adolescents. Therefore, the aim of our cross-sectional study was to study the prevalence of hyperuricaemia and dietary patterns in adolescents aged 13–16 years living in Yangzhou, China.MethodsAdolescents were asked to complete a 20-item food frequency questionnaire (FFQ) and provide an overnight fasting finger-prick sample. Principal component analysis (PCA) with varimax rotation was used to derive the dietary patterns that might be associated with high uric acid concentrations.ResultsA total of 1070 adolescents were recruited. Of these, 53.6% (n = 574) were females, and 58.5% (n = 625) were within the normal body mass index (BMI) range. The males had a significantly higher serving size and frequency in their weekly food consumption, including meat, poultry, Chinese cereal staple foods and Western-style fast foods, than the females (all p ConclusionsThe prevalence of hyperuricaemia was relatively high in Chinese adolescents. The prevention of hyperuricaemia measures should be strengthened in adolescents to effectively control for obesity and gout, which tend to persist into adulthood.

Thymidylate kinase (TMPK, EC2.7.4.9) is the enzyme that converts deoxythymidine monophosphate (dTMP) to deoxythymidine diphosphate (dTDP) in the synthesis of dTTP, an essential building block of DNA. To date, there is only one gene (

Background As real-world data resources expand and improve, there will increasingly be opportunities to study the effectiveness of interventions. There is a need to ensure that study designs explore potential sources of bias and either acknowledge or mitigate them, in order to improve the accuracy of findings. The objective of this study was to understand newly approved drug utilization patterns in real-world clinical settings over time. Methods This retrospective study included three sources of real-world data (claims, electronic health records, and recoded data from a quality care program) collected from patients diagnosed with gastric cancer who initiated therapy with either trastuzumab or ramucirumab. Linear regression was used to investigate trends in the use of these drugs for the care of patients with gastric cancer over time from Food and Drug Administration (FDA) approval. Results Eligible patients (n=1700) had consistent demographic and clinical characteristics over time. After regulatory approval, trastuzumab was used in later lines of therapy and then shifted to earlier lines (p=0.002), while ramucirumab utilization remained consistent over time after FDA approval (p=0.49). Ramucirumab augmentation, defined as the addition of the drug after initiation of a line of therapy, decreased over time (p=0.03), and trastuzumab augmentation remained consistent over time (p=0.58). Conclusion Since treatment effectiveness may change across lines of treatment, bias may arise if there are changes in the use of the drug (such as line migration) during the time period of analysis using real-world data.

The objective of this study was to examine the impact of cardiac structure and function at baseline on the outcomes associated with arteriovenous fistula (AVF) in patients on hemodialysis (HD). Patients who initiated HD aged ≥70 years and received a mature AVF creation were included retrospectively. Echocardiographic parameters measured within 1 week before AVF creation were acquired. The observational period for each patient was from the point of AVF creation to the last time of follow-up unless AVF abandonment or death occurred. Kaplan-Meier and Cox proportional hazard regression analyses were conducted. A total of 82 elderly Chinese HD patients with mature radiocephalic AVF (RCAVF) and EF ≥50% were analyzed. During the median study period of 26.8 (12-40) months, 42 (51.2%) experienced RCAVF dysfunction and 34 (41.5%) progressed to abandonment. Primary and cumulative patencies at 6, 12, 24, and 36 months were 81%, 73%, 48%, 38%, and 84%, 81%, 68%, 55%, respectively. Left ventricle end-diastolic volume (LVEDV) ≤103.5 mL (HR = 2.5, P = .019) and the right side of RCAVF (HR = 3.59, P = .003) significantly predicted RCAVF dysfunction. The main pulmonary artery internal diameter (MPAID) ≤21.5 mm (HR = 4.3, P = .001) as well as the right side (HR = 2.95, P = .047) were the independent predictors for RCAVF abandonment. In conclusion, LVEDV, MPAID assessed by echocardiography and the right side of RCAVF, showed significant predictive implications for the outcomes of RCAVF. Disparities among nationalities in the areas of utilization and patency of AVFs necessitate additional studies.

Objective The aim of this study was to validate the results of two Emanuel syndromes detected by non-invasive prenatal screening (NIPS) screening using invasive methods, providing clinical performance of NIPS on chromosome microduplication detection. Methods NIPS was performed to diagnose the Emanuel syndrome. Amniocentesis or cordocentesis was performed to confirm the positive screening result of Emanuel syndrome cases. Fetal sample was detected by karyotyping, fluorescence in situ hybridization (FISH), and single nucleotide polymorphism array (SNP Array). Parental karyotyping and FISH were also carried out. Results Two cases with chromosomal abnormalities of 11q23.3q25 and 22q11.1q11.21 were found by NIPS. Chromosomal karyotyping showed that the two fetuses each have a small supernumerary marker chromosome (sSMC), SNP Array further demonstrated double duplications approximately 18 Mb in 11q23.3q25 and 3 Mb in 22q11.1q11.21. FISH confirmed that the small supernumerary marker chromosome (sSMC) was ish der(22)t(11;22) (TUPLE1+, ARSA-). Ultrasound scan and MRI showed some structure malformations in two fetuses. The two mothers were found to be a balanced carrier: 46,XX, t(11;22)(q23.3;q11.2). Conclusion NIPS could effectively identify Emanuel syndrome, which may indicate risks of a parent being a balanced rearrangement carrier. The followed confirmation test for positive sample is necessary and ensures the accuracy of the diagnosis.

Purpose Clear cell renal cell carcinoma(ccRCC) is the most common type of renal cell carcinoma. While it is curable when detected at an early stage, some patients presented with advanced disease have poor prognosis. We aimed to identify key genes and miRNAs associated with clinical prognosis in ccRCC. Methods The microarray datasets were obtained from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMs) were analyzed by using GEO2R. Then, Functional enrichment analysis was performed using the DAVID. A retrospective series of 254 ccRCC patients with complete clinical information was included in this study. Kaplan-Meier analysis and multivariate cox regression analysis were used for prognostic analysis. Wound healing assay and transwell assay were designed to evaluate the migration and invasion ability of ccRCC cell lines. Results miRNA-18a was identified to be related with prognosis of ccRCC by using Kaplan-Meier analysis and multivariate cox regression analysis demonstrated that the prognostic value of miRNA-18a was independent of clinical features. Further studies showed that up-regulation of miRNA-18a had a positive effect on migration and invasion of ccRCC cells. The target gene (HIF1A) of the miRNA-18a was predicted by using the miRPathDB database. The transcription factors of DEGs were identified by using the i-cisTarget. Luckily, HIF1A was found to be one of the transcription factors of DEGs. Among these DEGs, PVT1 may be regulated by HIF1A and be related with prognosis of ccRCC. Finally, validation of miRNA18a/HIF1A/PVT1 pathway was checked via reverse transcription-polymerase chain reaction (RT-PCR) assay in both cell lines and clinical tumor samples. Conclusion Our research revealed that miRNA18a/HIF1A/PVT1 pathway might play a crucial role in ccRCC progression, providing novel insights into understanding of ccRCC molecular mechanisms. Importantly, miRNA-18a could serve as a potential diagnostic biomarker and therapeutic targets for ccRCC patients.

Our previous study revealed a higher incidence of gene dynamic mutation in newborns conceived by IVF, highlighting that IVF may be disruptive to the DNA stability of IVF offspring. However, the underlying mechanisms remain unclear. The DNA damage repair system plays an essential role in gene dynamic mutation and neurodegenerative disease. To evaluate the long-term impact of IVF on DNA damage repair genes, we established an IVF mouse model and analyzed gene and protein expression levels of MSH2, MSH3, MSH6, MLH1, PMS2, OGG1, APEX1, XPA and RPA1 and also the amount of H2AX phosphorylation of serine 139 which is highly suggestive of DNA double-strand break (γH2AX expression level) in the brain tissue of IVF conceived mice and their DNA methylation status using quantitative real-time PCR, western blotting and pyrosequencing. Furthermore, we assessed the capacity of two specific non-physiological factors in IVF procedures during preimplantation development. The results demonstrated that the expression and methylation levels of some DNA damage repair genes in the brain tissue of IVF mice were significantly changed at 3 weeks, 10 weeks and 1.5 years of age, when compared with the in vivo control group. In support of mouse model findings, oxygen concentration of in vitro culture environment was shown to have the capacity to modulate gene expression and DNA methylation levels of some DNA damage repair genes. In summary, our study indicated that IVF could bring about long-term alterations of gene and protein expression and DNA methylation levels of some DNA damage repair genes in the brain tissue and these alterations might be resulted from the different oxygen concentration of culture environment, providing valuable perspectives to improve the safety and efficiency of IVF at early embryonic stage and also throughout different life stages.

Efficient capture and storage of radioactive iodine isotopes are important in nuclear waste treatment and environmental protection. Coordination polymers (CPs) are a family of newly emerging potential iodine adsorbents. However, the exact structure–activity relationship between various structural CP hosts and their noncovalent adsorption effects toward iodine guest molecules has not been elucidated. Herein, a crystal engineering strategy was employed to systematically study the effects of porosity and arrangement of noncovalent interaction sites of CP hosts on the iodine uptake performance. Three isomeric CPs—{[Zn3(μ3-OH)(L)(H2O)3]·2H2O}n (1), {[Zn3(μ3-OH)(L)(H2O)]·2DMF·3H2O}n (2), and {[Zn3(μ3-OH)(L)(DMF)2]·H2O}n (3)—having different structures were synthesized from a π-electron-rich polycarboxylate ligand, H5L [5,5′-((5-carboxy-1,3-phenylene)bis(oxy))diisophthalic acid], containing potential sites for charge-transfer interaction and halogen bonding. CP 2, with a medium channel size and suitable arrangement of noncovalent interaction sites, exhibited higher I2 adsorption capacity than the other two CPs. The synergistic CO⋯I and charge-transfer π⋯I interactions between the I2 guest and the carboxylate moiety and the benzene ring of CP 2, respectively, were validated by X-ray diffraction analysis, electrochemical impedance spectroscopy, and solid-state fluorescence spectroscopy.

A series of isostructural lanthanide coordination polymers (Ln-CPs) formulated as [Ln(tcptpy)(H2O)2·2H2O]n {Ln3+ = Sm3+ (1), Eu3+ (2), Gd3+ (3), Tb3+ (4), Dy3+ (5); H3tcptpy = 4-(2,4,6-tricarboxylphenyl)-4,2':6',4''-terpyridine} has been afforded and characterized systematically. Their structures were established by single-crystal X-ray diffraction. All the complexes feature two dimensional (2D) layers with (4,4)-connected topology. By virtue of the isostructural frameworks, a family of binary co-doped Ln-CPs [Tb1-xEuxtcptpy]n was achieved for ratiometric temperature sensors, among which Tb0.897Eu0.103tcptpy exhibits a good linear response to the temperature range from 305-340 K, with a maximum relative sensitivity (Sm) of 8.41% K-1 at 340 K. Moreover, Tb-CPs exhibit excellent applications as luminescent sensors for the detection of nitrobenzene and Fe3+ cations with high selectivity and sensitivity based on a luminescence quenching approach. The possible mechanisms of the fluorescence quenching effect were also investigated.

Dried fruits of black goji were investigated for their fatty acid, mineral contents, and antioxidant activity against isoproterenol‐induced acute myocardial ischemia in mice was revealed. It was observed that the key fatty acids from Lycium ruthenicum Murr. (LRM) oil studied included linoleic (59.38%), oleic (20.85%), palmitic (7.07%), linolenic (2.98%), and stearic acids (5.31%), which together comprised 95.59% of the total fatty acids. The key mineral nutrients studied were potassium (17,631.15 mg/kg), calcium (2004.4 mg/kg), and magnesium (1,274.6 mg/kg), while copper, iron, manganese, and zinc were found in trace. Moreover, oral administration of water extraction of LRM exhibited significant reduction of enzyme activities, and MDA level triggered by ISO to be near normal level, while exhibited a significant increase of SOD and GSH activities. Our results provide deep insight on LRM as a potential source of high‐value phytochemicals for the development of new functional food and beverage products., Lycium ruthenicum nutrient content not determined yet including mineral and fatty acid was investigated. The whole crude water extract was also investigated for its antioxidant activity against acute myocardial ischemia in mice.

Metal ions play an important role in many metabolic processes in all living organisms. At low concentrations, heavy metals such as Fe

Landscape morphology is a significant area of landscape architecture research. One of the scientific and technological issues in recent landscape morphology research is the use of quantitative analysis technology driven by morphology indexes and computational models to describe, compare, and analyze form features. This article focuses on the form features of the polder landscape, based on existing theoretical and practical achievements in landscape morphology. First, we choose five landscape morphology indexes based on the morphological constituent units of the landscape (elongation, rectangular compactness, concavity, ellipse compactness, and fractal dimension). Then, using the self-organizing map (SOM), we create an identification model for clustering the types of constituent units. The experimental results show that the identification model can classify polder morphology and analyze the distribution of units using typical polders in the Yangtze River’s south bank as study cases. This article presents a technical approach to polder landscape morphology classification as well as a reference and developable quantitative analysis method for landscape morphology research.

Nucleotide metabolism is a complex pathway regulating crucial cellular processes such as nucleic acid synthesis, DNA repair and proliferation. This study shows that impairment of the biosynthesis of one of the building blocks of DNA, dTTP, causes a severe, early-onset neurodegenerative disease. Here, we describe two unrelated children with bi-allelic variants in DTYMK, encoding dTMPK, which catalyzes the penultimate step in dTTP biosynthesis. The affected children show severe microcephaly and growth retardation with minimal neurodevelopment. Brain imaging revealed severe cerebral atrophy and disappearance of the basal ganglia. In cells of affected individuals, dTMPK enzyme activity was minimal, along with impaired DNA replication. In addition, we generated dtymk mutant zebrafish that replicate this phenotype of microcephaly, neuronal cell death and early lethality. An increase of ribonucleotide incorporation in the genome as well as impaired responses to DNA damage were observed in dtymk mutant zebrafish, providing novel pathophysiological insights. It is highly remarkable that this deficiency is viable as an essential component for DNA cannot be generated, since the metabolic pathway for dTTP synthesis is completely blocked. In summary, by combining genetic and biochemical approaches in multiple models we identified loss-of-function of DTYMK as the cause of a severe postnatal neurodegenerative disease and highlight the essential nature of dTTP synthesis in the maintenance of genome stability and neuronal survival.

SciApps is an open-source, web-based platform for processing, storing, visualizing, and distributing genomic data and analysis results. Built upon the Tapis (formerly Agave) platform, SciApps brings users TB-scale of data storage via CyVerse Data Store and over one million CPUs via the Extreme Science and Engineering Discovery Environment (XSEDE) resources at Texas Advanced Computing Center (TACC). SciApps provides users ways to chain individual jobs into automated and reproducible workflows in a distributed cloud and provides a management system for data, associated metadata, individual analysis jobs, and multi-step workflows. This chapter provides examples of how to (1) submitting, managing, constructing workflows, (2) using public workflows for Bulked Segregant Analysis (BSA), (3) constructing a Data Analysis Center (DAC), and Data Coordination Center (DCC) for the plant ENCODE project.

Background Pancreatic cancer remains one of the most lethal cancers largely due to the inefficient delivery of therapeutics. Nanomaterials have been extensively investigated as drug delivery platforms, showing improved drug pharmacodynamics and pharmacokinetics. However, their applications in pancreatic cancer have not yet been successful due to limited tumor delivery caused by dense tumor stroma and distorted tumor vasculatures. Meanwhile, smaller-sized nanomaterials have shown improved tumor delivery and retention in various tumors, including pancreatic tumors, suggesting their potential in enhancing drug delivery. Methods An ultrafine iron oxide nanoparticle (uIONP) was used to encapsulate 7-ethyl-10-hydroxyl camptothecin (SN38), the water-insoluble active metabolite of chemotherapy drug irinotecan for treating pancreatic cancer in clinic. Insulin-like growth factor 1 (IGF-1) was conjugated to uIONP as a ligand for targeting pancreatic cancer and stromal cells overexpressing IGF-1 receptor (IGF1R). The SN38 loading and release profile were characterized. The cancer cell targeting and induced apoptosis by developed nano-formulationIGF1-uIONP/SN38 were also investigated. Results IGF1-uIONP/SN38 demonstrated stable drug loading in physiological pH with the loading efficiency of 68.2 ± 3.5% (SN38/Fe, wt%) and

Metal ions play an important role in many metabolic processes in all living organisms. At low concentrations, heavy metals such as Fe2+, Cu2+ and Zn2+ are essential cofactors for many enzymes. However, at high concentrations they are toxic. Mesorhizobium species belong to the class alpha-proteobacteria and have high tolerance to soil acidity, salinity, temperature extremes, and metallicolous conditions. To identify factors responsible for this tolerance we have studied the effects of metal ions on Mesorhizobium delmotii thymidylate kinase (MdTMPK), an essential enzyme in the synthesis of dTTP, thus being vital for cell growth. We show that Mg2+ and Mn2+ are the divalent metal ions required for catalysis and that Mn2+ gives the highest catalytic efficiency. MdTMPK activity in the presence of Mg2+ was strongly inhibited by the co-presence of Zn2+, Ni2+ and Co2+. However, the addition of Cs+ caused >2-fold enhanced MdTMPK activity. For TMPK from Bacilus anthracis and humans, the effects of Mg2+ and Mn2+ were similar, whereas the effects of other divalent metal ions were different, and no stimulatory effect of Cs+ was observed. Together, our results demonstrate that MdTMPK and BaTMPK function well in the presence of high concentrations of heavy metal ions, introducing a potential contribution of these enzymes to the heavy metal tolerance of Mesorhizobium delmotii and Bacillus anthracis

Due to people’s increasing dependence on software, the emergence of software defects will lead to serious consequences. And the essential cause of software defects is the increasing complexity of software. The premise of reducing software defects is to understand the software topology to ensure software quality. The software topology refers to the connection between the internal elements of the software, and it has become an important factor affecting the quality of the software. In this paper, we use complex network theory as a tool to analyze the software topology. Firstly, we extract the software structural information from the source code of the software system and abstract the extracted software structural information with software network theory. Secondly, the metrics widely used in complex networks are introduced to analyze the built software network. When tracking the values of these metrics in the software system, we have a deeper understanding of the software topology. These results provide a different dimension to understanding the software topology, which has important guiding significance for the subsequent understanding of the software and is also very useful for reducing software defects and ensuring software quality.

Twisted van der Waals heterostructures were recently found to possess unique physical properties, such as superconductivity in magic angle bilayer graphene. Owing to the nonhomogeneous stacking, the energy of twisted van der Waals heterostructures are often higher than their AA or AB stacking counterpart, therefore, fabricating such structures remains a great challenge in experiments. On the other hand, one dimensional (1D) coaxial van der Waals structures has less freedom to undergo phase transition, thus offer opportunity for fabricating the 1D cousin of twisted bilayer graphene. In this work, we show by molecular dynamic simulations that graphene nanoribbons can self-assemble onto the surface of carbon nanotubes driven by van der Waals interactions. By modifying the size of the carbon nanotubes or graphene nanoribbons, the resultant configurations can be controlled. Of particular interest is the formation of twisted double walled carbon nanotubes whose chiral angle difference can be tuned, including the 1.1° magic angle. Upon the longitudinal unzipping of such structures, twisted bilayer graphene nanoribbons can be obtained. As the longitudinal unzipping of carbon nanotubes is a mature technique, we expect the strategy proposed in this study to stimulate experimental efforts and promote the fast growing research in twistronics.

A neural network based on a word or character embedding is a mainstream model framework in text sentiment analysis and has achieved good results. However, there is a lack of learning about POS-Tagging and Sequence-Tagging. In this research, we propose a multifeature text data-augmentation model (M-DA) with a multiple-input single-output network structure to overcome this problem of Chinese text sentiment analysis. First, this paper sequentially obtains various sequences of Chinese text, including word sequence, pos sequence, char sequence, char_pos sequence, and char_4tag sequence, we use char_pos and the char_4tag to construct a new sequence (4tag_pos) and then use 4tag_pos to mark the characters to obtain the reconstructed characters sequence (char_4tag_pos), so as to achieve the purpose of text enhancement. Then, the Word2Vec method is used to train the initial reconstruction of the character embedding. Finally, the BiLSTM network is used to capture the long-term dependence between the sequences, and the dropout technology and attention are used to improve the accuracy. In the course of the experiment, we also realized that it is better to use the original sequence and the sequence after text enhancement technology as the input of the BiLSTM network. Therefore, our proposed model also discusses the concatenate or dot method to fuse multiple sequences as the final embedding. Multigroup comparison experiments are conducted on the data set, and the results show that the proposed M-DA model is superior to the traditional deep learning technology in terms of accuracy, recall rate, f-measure, and accuracy, and the relative time cost is small.

In order to investigate the value of the ultrasonic monitoring of maternal and fetal vascular parameters, serum vitamin D, and placental growth factor (PLGF) in predicting fetal growth restriction (FGR), a method of ultrasonic detection of genetic factors causing fetal growth in utero was proposed. 125 pregnant women with FGR diagnosed in our hospital from June 2018 to June 2021 (the FGR group) and 125 pregnant women with a normal prenatal examination (the control group) were collected retrospectively. The systolic/diastolic blood flow ratio (S/D), pulsatile index (PI), and resistance index (RI) of the fetal umbilical artery (UA), middle cerebral artery (MCA), and maternal uterine artery (UtA) were monitored by ultrasound at 20 to 24 weeks of gestation, and the levels of serum vitamin D and PLGF were detected. The receiver operating characteristic curve (ROC curve) was used to evaluate the predictive value of FGR. The results showed that the S/D, PI, and RI of UA in the FGR group were higher than those in the control group, the areas under the curve (AUC) were 0.866, 0.817, and 0.849, and the sensitivity and specificity were (72.8%, 91.2%), (50.4%, 100%), and (72.8%, 91.2%), respectively. The S/D, PI, and RI of MCA were lower than those of the control group. The AUC was 0.882, 0.869, and 0.834, respectively; the sensitivity and specificity were (92.0%, 74.4%), (88.8%, 81.6%), and (90.4%, 72%), respectively. The S/D, PI, and RI of UtA were higher than those of the control group; the AUC was 0.768, 0.729, and 0.732; the sensitivity and specificity were (91.2%, 52%), (48%, 90.4%), and (48.8%, 90.4%), respectively. The serum levels of vitamin D and PLGF were lower than those of the control group (AUC 0.784 and 0.807), and the sensitivity and specificity were (54.4%, 91.2%) and (99.2%, 52%), respectively. It was concluded that the ultrasound monitoring of UA, MCA, and UtA in pregnant women in the middle of pregnancy and detection of serum vitamin D and PLGF levels had a certain predictive value for FGR. Moreover, the comprehensive evaluation could reduce the occurrence of FGR in high-risk pregnant women.

Thymidylate kinase (TMPK) phosphorylates deoxythymidine monophosphate (dTMP) and plays an important role in genome stability. Deficiency in TMPK activity due to genetic alterations of DTYMK, i.e., the gene coding for TMPK, causes severe microcephaly in humans. However, no defects were observed in other tissues, suggesting the existence of a compensatory enzyme for dTTP synthesis. In search for this compensatory enzyme we analyzed 6 isoforms of TMPK mRNA deposited in the GenBank. Of these, only isoform 1 has been characterized and represents the known human TMPK. Our results reveal that isoform 2, 3, 4 and 5 lack essential structural elements for substrate binding and, thus, they are considered as nonfunctional isoforms. Isoform 6, however, has intact catalytic centers, i.e., dTMP-binding, DRX motif, ATP-binding p-loop and lid region, which are the key structural elements of an active TMPK, suggesting that isoform 6 may function as TMPK. When isoform 6 was expressed and purified, it showed only minimal activity (